Different loop arrangements of intramolecular human telomeric (3+1) G-quadruplexes in K+ solution.

Different loop arrangements of intramolecular human telomeric (3+1) G-quadruplexes in K+ solution.
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K+溶液中分子内人端粒(3+ 1)G-四链体的不同环排列。

DOI:
10.1093/nar/gkl726
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发表时间:
2006
影响因子:
14.9
通讯作者:
Patel, Dinshaw J.
Patel, Dinshaw J.
中科院分区:
生物学2区
文献类型:
--
作者:
Phan, Anh Tuan;Luu, Kim Ngoc;Patel, Dinshaw J.

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人类端粒富含G链形成的分子内G-四链体是很有希望的抗癌靶点。在这里,我们证明了四个重复的人类端粒DNA序列在K+溶液中可以采用两个不同的分子内G-四链折叠。这两个结构都含有(3+1)G-四分体核心,其中三个G-轨迹朝一个方向,第四个方向相反,有一个双链反转和两个边环,但涉及不同的环排列。这一结果表明了(3+1)核心G-四链拓扑的稳健性,从而表明它是基于结构的药物设计的重要平台。我们的数据也支持多个人类端粒G-四链构象在K+溶液中共存的观点。此外,即使侧翼序列的微小变化也可能扰乱共存的不同G-四链形式之间的平衡。
Intramolecular G-quadruplexes formed by the human telomeric G-rich strand are promising anticancer targets. Here we show that four-repeat human telomeric DNA sequences can adopt two different intramolecular G-quadruplex folds in K+ solution. The two structures contain the (3+1) G-tetrad core, in which three G-tracts are oriented in one direction and the fourth in the opposite direction, with one double-chain-reversal and two edgewise loops, but involve different loop arrangements. This result indicates the robustness of the (3+1) core G-quadruplex topology, thereby suggesting it as an important platform for structure-based drug design. Our data also support the view that multiple human telomeric G-quadruplex conformations coexist in K+ solution. Furthermore, even small changes to flanking sequences can perturb the equilibrium between different coexisting G-quadruplex forms.
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影响因子: 14.9
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